Nicotine infusion modulates immobilization stress-triggered induction of gene expression of rat catecholamine biosynthetic enzymes

作     者：Serova, L Danailov, E Chamas, F Sabban, EL 

作者机构：New York Med Coll Dept Biochem & Mol Biol Valhalla NY 10595 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第291卷第2期

页      面：884-892页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NINDS NIH HHS [NS32166] Funding Source: Medline 

主　　题：肾上腺髓质/药物作用 肾上腺髓质/酶学 儿茶酚胺类/生物合成 中枢神经系统/药物作用 中枢神经系统/酶学 皮质酮/血液 多巴胺β羟化酶/遗传学 混合功能氧化酶类/遗传学 神经肽类/遗传学 尼古丁/投药和剂量 尼古丁/药理学 苯基乙醇胺N-甲基转移酶/遗传学 原癌基因蛋白质c-fos/代谢 RNA 信使/代谢 大鼠 Sprague-Dawley 无特异性病原体有机物 应力 物理 酪氨酸单氧化酶/遗传学 动物 男(雄)性 大鼠 

摘      要：The relationship between nicotine and stress is complex and paradoxical. Although people claim they smoke because it relaxes them, nicotine can trigger some of the effects observed with stress, including the release and synthesis of the catecholamines and their biosynthetic enzymes. This study examined one aspect of this confusing relationship between nicotine and stress. Multiple injections of nicotine bitartrate (5 mg/kg) elevated mRNA levels for the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase, and of preproneuropeptide Y in rat adrenal medulla more than did 1 mg/kg of nicotine bitartrate. In the locus ceruleus, substantia nigra, and ventral tegmental area both doses equally induced TH mRNA levels. Nicotine infusion (15 mg/kg/day) did not affect adrenal mRNA levels for any of the genes of interest and did not increase plasma corticosterone levels. However, in rats preexposed to nicotinic infusions, the response to a single immobilization (IMO) stress was markedly attenuated with respect to changes in adrenomedullary TH, DBH, and phenylethanolamine N-methyltransferase mRNA levels and in c-Fos protein levels. In the central nervous system, the chronic infusion of nicotine prevented the induction of TH mRNA by repeated IMO stress in the ventral tegmental area (but not in substantia nigra) and of DBH mRNA by single IMO in the locus ceruleus. These findings may explain some of the complex interactions between stress and exposure to nicotine.